Targeting the extracellular matrix for NF1-associated neurofibroma treatment

Neurofibromatosis type 1(NF1)is one of the most common genetic disorders that predisposes patients to benign and malignant tumors of the peripheral nervous system.Plexiform and cutaneous neurofibromas are NF1-associated benign tumors.Despite their benign nature,they can cause tremendous morbidity in patients with NF1.Therapeutic drug options are limited to the MEK inhibitor,selumetinib,which is the only approved drug for pediatric patients with plexiform neurofibromas.Antifibrotic strategies have substantial therapeutic potential for NF1-associated neurofibromas.This review discusses the fibrotic features of plexiform and cutaneous neurofi-bromas focusing on the pathological composition of the extracellular matrix.It also highlights the core pathways implicated in the biochemical and biophysical regulation of the extracellular matrix remodeling in tumor imitation and progression.Finally,this review provides a brief outlook on how exploring novel vulnerabilities residing in the aberrant extracellular matrix and their underlying pathways can benefit the treatment of NF1-associated neurofibromas.

Volumetric measurement techniques for assessment of cutaneous neurofibromas:A review

Cutaneous neurofibroma(cNF)is a prevalent clinical manifestation of neurofibromatosis type 1,significantly affecting the well-being and quality of life of the affected individuals.The adoption of reliable and reproducible volumetric measurement techniques is essential for precisely evaluating tumor burden and plays a critical role in the development of effective treatments for cNF.This study focuses on widely used volumetric measurement techniques,including vernier calipers,ultrasound,computed tomography,magnetic resonance imaging,and three-dimensional scanning imaging.It outlines the merits and drawbacks of each technique in assessing the cNF load,providing an overview of their current applications and ongoing research advancements in this domain.

Solitary intraosseous neurofibroma in the mandible mimicking a cystic lesion:A case report and review of literature

BACKGROUND Neurofibromas are benign tumors of a neurogenic origin.If these tumors occur without any other signs of neurofibromatosis,they are classified as isolated neurofibromas.Neurofibromas in the oral cavity mostly occur within soft tissues,indicating that solitary intraosseous neurofibromas in the mandible are rare.Due to the absence of specific clinical manifestations,early diagnosis and treatment of these tumors are difficult to achieve.CASE SUMMARY A 37-year-old female patient visited our hospital due to numbness and swelling of the gums in the right lower molar area that had persisted for half a month.The patient’s overall condition and intraoral examination revealed no significant abnormalities.She was initially diagnosed with a cystic lesion in the right mandible.However,after a more thorough examination,the final pathological diagnosis was confirmed to be neurofibroma.Complete tumor resection and partial removal of the right inferior alveolar nerve were performed.As of writing this report,there have been no signs of tumor recurrence for nine months following the surgery.CONCLUSION This case report discusses the key features that are useful for differentiating solitary intraosseous neurofibromas from other cystic lesions.

Solitary colonic neurofibroma in a patient with transient segmental colitis: Case report

Neurofibromas of the large bowel are very rare and usually are part of the colonic involvement in neurofibromatosis type 1 （Nf1, yon Recklinghausen＇s disease）. Solitary neurofibromas of the colon are extremely rare. We describe a case of an isolated neurofibroma that was found in the large bowel of a patient who suffered from segmental colitis and presented with bloody diarrhea. A review of the literature is also included, concerning the disclosure of isolated neurofibromas in the gut and other body parts and the type of gastrointestinal involvement in von Recklinghausen＇s disease.

Isolated colonic neurofibroma in the setting of Lynch syndrome:A case report and review of literature

BACKGROUND Gastrointestinal neurofibromas are commonly found in patients diagnosed with neurofibromatosis type 1.However,isolated gastrointestinal neurofibromas are a rare entity and only fourteen cases of isolated colorectal neurofibromas have been documented in literature.Isolated gastrointestinal neurofibromas have not been associated with Lynch syndrome(LS).Patients with LS are at an increased risk of colorectal cancer,and are recommended to undergo screening colonoscopy.CASE SUMMARY A 33-year-old healthy female with a family history of LS was found to have unresectable polyp in the ascending colon on screening colonoscopy suspicious for malignancy.The patient was asymptomatic and had no stigmata of neurofibromatosis.A staging workup for colorectal cancer revealed no evidence of metastatic disease.A discussion with the patient resulted in the decision to undergo a segmental resection with ongoing surveillance.The patient underwent a laparoscopic right hemicolectomy.Histopathology was consistent with a gastrointestinal neurofibroma.Post-operatively,the patient recovered well.She will not require further treatment with regards to her colonic neurofibroma,but will continue to follow-up for ongoing surveillance of her LS.CONCLUSION We present the first case of an isolated colonic neurofibroma in a patient with LS.This case explores considerations for the management of isolated gastrointestinal neurofibromas given the lack of guidelines in literature.

Isolated colonic neurofibroma, a rare tumor: A case report and review of literature

BACKGROUND Neurofibromas are tumors comprised of peripheral nerve sheath and connective tissue components.They can occur sporadically or as part of familial syndromes such as neurofibromatosis type 1.Isolated colonic neurofibroma without systemic manifestations is a rarely reported clinical entity.Here we present a case of a 51 years old male with an isolated colonic neurofibroma seen on a screening colonoscopy.CASE SUMMARY Fifty-one years old male who was otherwise healthy without a significant family history of cancer underwent a screening colonoscopy and was found have a 2.3 cm×1.4 cm lesion in the colon.Tissue biopsy revealed a spindle cell tumor.Magnetic resonance imaging of the pelvis was negative for adenopathy.He underwent an endoscopic ultrasound that showed an ill-defined avascular lesion of mixed echogenicity measuring 2.8 cm×15.2 cm in the submucosa with no communication with muscularis mucosa or propria.Immunohistochemistry staining of the tumor was strongly positive for S100,with rare penetrating axons deep within the tumor.Tumor cells were negative for c-kit and desmin and had low Ki-67 index.These findings were consistent with a solitary colonic submucosal neurofibroma.A detailed history and physical examination did not reveal any evidence of extraintestinal neurofibromatosis.He underwent transanal surgical resection of the tumor.The patient tolerated the procedure well without any complications.CONCLUSION While neurofibromas have been well described in literature,an isolated colonic neurofibroma is a rare pathological entity.Malignant transformation of neurofibromas has been reported in patients with neurofibromatosis syndromes.We report a case of isolated colonic neurofibroma and highlight the importance of resection due to the increased risk of tumorigenesis.

Solitary plexiform neurofibroma of the stomach:A case report

Plexiform neurofibroma(PN)of the digestive tract is very rare and usually part of the generalized syndrome of neurofibromatosis type 1(von Recklinghausen disease).Solitary PN of the stomach is extremely rare and has not been reported in the literatures.Here we present a case of solitary PN of the stomach,which was not associated with von Recklinghausen disease.A38-year-old male presented abdominal pain and distention for 7 d.The patient underwent endoscopy of the upper gastrointestinal tract,which revealed a 3.5 cm protruding and cauliflower-shaped mass with a shallow1 cm central ulcer in the greater curvature of the stomach.The lesion was removed by laparoscopic surgery.Histological examination demonstrated characteristic histological findings of spindle-shaped cells.Immunohistochemical analysis showed that the tumor cells were positive for S-100 protein,but negative for CD34,KI-67,CD117,and actin.Based on histological findings,gastrointestinal stromal tumor could be excluded,and thus the case was confirmed as PN.We described the clinical features,physical examination,endoscopic findings,and histopathological examination of this case.

Giant Mediastinal Neurofibroma in a Child with Neurofibromatosis Type I

Aim: There are a variety of malignant tumors related to neurofibromatosis type 1 (NF1). This report describes a rare pediatric NF1 case with an unresectable giant mediastinal tumor. Case: A 6-year-old girl with wheezing was admitted to our institution for the further evaluation of a right mediastinal mass on plain chest radiography. On examination, there were multiple café au lait spots mainly on the trunk, and a well-defined, immobile, painless mass was palpable on her neck. The mediastinal lesion was detected as nonuniform mass surrounding the aortic arch, pulmonary artery, and right main bronchus on the contrast-enhanced CT and MRI. Open biopsy was useful to rule out malignancy and revealed neurofibroma, and contributed to follow up and treatment. Discussion: Open biopsy was useful to rule out malignancy, such as malignant peripheral nerve sheath tumor, revealed neurofibroma, and also contributed to follow up and treatment. The authors report successful management by open biopsy and discuss several clinical points regarding mediastinal neurofibroma for NF1.

A Proof-of-Concept Assessment of the Safety and Efficacy of Intralesional Diclofenac in the Treatment of Cutaneous Neurofibromas

The objectives of this study were to assess the safety and efficacy of intralesionally administered diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. This was a proof-of-concept, prospective, safety and efficacy study of the effect of intralesionally administered diclofenac 25 mg/ml given once a week to 3 target cutaneous neurofibromas for 4 consecutive weeks. Overall, there was no significant change in neurofibroma size. During the study, some treated lesions developed signs of necrosis and fell off after a few weeks, but none of the control neurofibromas fell off. There were no significant changes in patient’s vital signs. A few adverse events occurred, mostly at the injection sites. During the study, some neurofibromas developed necrosis after the diclofenac injections and eventually detached from the patient. Overall, diclofenac was well tolerated, suggesting minimal systemic exposure, which required confirmation and further studies, including bioavailability analysis.

Plexiform neurofibroma of the cauda equina with follow-up of 10 years:A case report

BACKGROUND Plexiform neurofibromas are extremely rarely found in the region of cauda equina and can pose a significant challenge in the diagnostic and management sense.To our knowledge,only 7 cases of cauda equina neurofibromatosis(CENF)have been reported up-to-date.CASE SUMMARY We describe a case of a 55-year-old man with a 10 years history of progressive lower extremities weakness and bladder dysfunction.Before presenting,patient was misdiagnosed with idiopathic polyneuropathy.Lumbar spine MRI revealed a tortuous tumorous masses in the cauda equina region,extending through the Th12-L4 vertebrae.The patient underwent Th12-L3 Laminectomy with duraplasty.During the operation,the most enlarged electroneurographically silent nerve root was resected,anticipating inadequate decompression if nerve root was spared.The patient’s neurological condition improved post-operatively,but urinary retention became the major complaint.We provide a follow-up period of 10 years.During this time,the patient’s condition progressively worsened despite extensive decompression.The consequent MRI scans showed progressive enlargement of cauda equina roots and increasing lumbar stenosis,predominantly affecting L3-L4 segment.During the follow-up 8 years after the operation,the patient complained of worsening lower extremities sensorimotor function and neurogenic claudication.Subsequent MRI revealed lumbar spine stenosis at the level of L3-L4,requiring further decompression.The patient underwent a second surgery involving L4-L5 Laminectomy with duraplasty and L2-L5 transpedicular fixation.The post-operative period was uneventful.Latest follow-up 18 mo after the second surgery revealed substantial improvement in patient’s well-being.CONCLUSION CENF should be kept in mind during the differential diagnostic work-up for polyneuropathies.Management with an extensive decompression,duraplasty and primary spinal fixation represents a rational approach to achieve a sustained symptomatic improvement and superior overall outcome.

Multiple neurofibromas plus fibrosarcoma with familial NF1 pathogenicity:A case report

BACKGROUND Neurofibromatosis(NF)is a genetic disease consisting of seven types,of which types 1 to 4 are caused by a dominant autosomal gene mutation;such disease sometimes arises in patients with NF type 1.However,it remains unclear whether the origin of neurofibrosarcoma is directly linked to the incidence of NF type 1,as no reports have been published on this issue.Here,we report a case of NF1-positive multiple neurofibromas with malignant fibrosarcomatous transformation in the pleural cavity.CASE SUMMARY A 51-year-old male was admitted to our hospital due to fever accompanied by coughing,chest tightness and asthma for more than one month.The preliminary diagnosis was NF type 1,which was pathologically confirmed by a subsequent thoracoabdominal subcutaneous biopsy.The definitive diagnosis was neurofibrosarcoma with a pathogenic NF1 gene.The patient refused surgery and chemoradiotherapy,and died two months later.NF is a genetic disease consisting of seven types,of which types 1 to 4 are caused by a dominant autosomal gene mutation.The case reported belongs to the class of NF1-positive dominant inheritance.Neurofibrosarcoma is a malignant tumor derived from cells surrounding the peripheral nerves.However,due to the lack of previous reports,it remains unclear whether the origin of neurofibrosarcoma is directly linked to the incidence of NF type 1.CONCLUSION We report the first case of NF1-positive multiple neurofibromas with malignant fibrosarcomatous transformation in the pleural cavity.

Neurofibroma of the Pinna

Neurofibromas are relatively common lesions of the nervous system, but only a few cases involving the pinna have been reported. Isolated neurofibroma of pinna without neurofibromatosis has not been reported in the literature so far. Neurofibromas may develop anywhere in the body, including cranial and peripheral nerves. The type of impairment associated with neurofibromas depends largely on the site of the lesion. Cutaneous lesions, especially in the head and neck, generally cause deformity, whereas lesions that affect deeper systems (e.g., the auditory and ocular systems) are more likely to cause functional impairment. Usually found in individuals with neurofibromatosis, we report a case of neurofibroma of pinna in a patient without

Neurofibroma discharged from the anus with stool:A case report and review of literature

Isolated neurofibromas that affect the gastrointestinal tract are rare and almost always manifest as neurofibro-matosis type 1 or multiple endocrine neoplasia type 2 b. In this paper, we present a case of a 24--year--old female with abdominal pain who discharged a neurofibroma in her stool without any blood on it. A colonoscopy showed multiple small polyps in the sigmoid colon and a nodule in the ileocecus. The pathology results and the immunohistochemical stains of the removed neoplasm from the ileocecus confirmed the diagnosis was a bowel neurofibroma. We report a rare case of ileocecal neurofibroma due to the patient's affected gastrointestinal tract, without any associated systemic syndrome other than a neurofibroma discharged in the stool.

Multiple recurrent neurofibromas in the abdominal wall:A case report

BACKGROUND Neurofibroma can be a clinical manifestation of neurofibromatosis,which is a benign neurogenic tumor that occurs sporadically.Neurofibromas in the abdomen usually appear in the retroperitoneal space.Reports on neurofibromas in the abdominal wall are rare,and multiple recurrent neurofibromas in this area have not yet been reported.CASE SUMMARY This is a case of a 73-year-old man who suffered from multiple recurrent neurofibromas in the abdominal wall for 16 years and received 13 surgical treatments.CONCLUSION We need to pay due attention to its treatment,and primary surgery should be designed thoroughly.

Solitary Intraparotid Facial Nerve Plexiform Neurofibroma

Solitary intraparotid facial nerve plexiform neurofibromas are extremely rare. These tumors arise from Schwann cells. The plexiform variant is recognized by tortuous and multinodular gross and microscopic lesions. It has a high risk of malignant transformation. We report a case of a solitary plexiform neurofibroma in a 5-year-old Italian male, who initially presented a right parotid mass of four-month duration. He had not pain, trismus, facial weakness or previous trauma. There was not familiar history of Von Recklinghausen’s disease. TC and MRI scans revealed a mass in the superficial lobe of the parotid gland. A partial parotidectomy was performed. Histopatological examination indicated plexiform neurofibroma. The incidence, presentation, diagnosis and surgical treatment of this lesion are discussed. In our case, the tumor could be readily separated from the main trunk, and facial movement was completely preserved owing to the rich neural network around the mass.

Laryngeal myxoid neurofibroma misdiagnosed as myxoma:a case report

Neurogenic tumours constitute a very small percentage of all neoplastic lesions of the head and neck region. Neurogenic tumors of the larynx are extremely rare. Two types of neurogenic tumors must be distinguished: Schwannomas and neurofibromas. Neurofibromas arise from the sheath of nerve fibers and are characterized by prominent collagen produc- tion and trapped nerve fibers. In the larynx, the most common sites of origin are arytenoids and aryepiglottic folds. Because of benign nature of this tumor, conservative surgery is recommended as the management of choice. Only few cases of laryngeal myxoid neurofibroma have been reported in literature and this article presents one case of laryngeal myxoid neurofibroma, which at first was misdiagnosed as myxoma, with brief review of literatures.

Plexiform Neurofibroma of Nasal Tip

Neurogenic tumor is the name given to any tumor that arises from the nerve tissue or its coverings. Neurogenic tumors of Sino-nasal cavity are a very rare entity. The most common types are Schwannomas and Neurofibromas and the plexiform subtype is one form of these neuroendocrine tumors. We report the case series of two such cases of a plexiform neurofibroma of the nasal tip, which were excised via an open rhinoplasty approach.

Giant mesenteric neurofibromas:a case report

We presented a case of giant neurofibromas arising from the jejunal mesentery of a 52-year-old man. The patient presented with epigastric fullness, and decrease of food intake, but without stigmata of neurofibromatosis-l. Ultrasonography, computed tomography （CT） and MR imaging revealed two large masses in the abdomen extending to the pelvis. Total resection of the tumors together with corresponding segments of intestines was performed. Histological examination and immunocytochemistry for S-100 protein confirmed the masses to be multiple neurofibromas of the mesentery. We also discussed the clinical features, and treatment approaches of similar cases in literatures.

A case of 25-year-old giant neurofibromatosis

In this paper,the authors presented a case report of a 39-year-old man taken to the Emergency Unit with a 25-year-old giant neurofibromatosis.Moreover,the treatment applied for this case and the physiopathology of the neurofibromatosis disease are also discussed.

腹膜后以脂肪成分为主的弥漫型神经纤维瘤1例并文献复习

目的探讨腹膜后弥漫型神经纤维瘤(DNF)的影像及病理表现。方法对1例经手术病理证实为腹膜后巨大DNF的影像学表现及病理资料进行回顾性分析,并复习相关文献。结果CT和MRI可见腹膜后以脂肪成分为主的巨大孤立性肿块,边界不清,其内散在多发团状实性成分,腹膜后大血管受压迫、包埋。实性成分在增强MRI上轻度强化,PET上代谢轻度增高。免疫组化上S-100、SOX-10均为阳性。结论DNF可发生在腹膜后,其临床和影像表现无明显特异性,确诊需要依靠病理组织学检查。